Imaging markers for Alzheimer disease
Which vs how
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Abstract
Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on which marker (i.e., amyloid imaging, 18F-fluorodeoxyglucose [FDG]-PET, SPECT, MRI) as well as how it is measured (“metric”: visual, manual, semiautomated, or automated segmentation/computation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR+ (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR+ of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR+ and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR+ from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11% and 18% of diagnostic and prognostic variance of LR+ and 16% and 24% of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13% and 62% of diagnostic and prognostic variance of LR+, and 29% and 18% of LR−. Within markers, the largest proportion of diagnostic LR+ and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials.
GLOSSARY
- AA=
- Alzheimer's Association;
- AD=
- Alzheimer disease;
- ANOVA=
- analysis of variance;
- FDG=
- fluorodeoxyglucose;
- ISTAART=
- International Society to Advance Alzheimer's Research and Treatments;
- LR=
- likelihood ratio;
- MCI=
- mild cognitive impairment;
- NIA=
- National Institute on Aging;
- NINCDS-ADRDA=
- National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association;
- npMCI=
- nonprogressed mild cognitive impairment;
- pMCI=
- progressed mild cognitive impairment;
- sc-SPM=
- single-case statistical parametric mapping;
- SOP=
- standard operating procedure
Footnotes
ISTAART's NeuroImaging Professional Interest Area contributors are listed on the Neurology® Web site at www.neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received November 20, 2012.
- Accepted in final form April 12, 2013.
- © 2013 American Academy of Neurology
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